1. Field of the Art
This invention relates to apparatus for the determination of biomass in a culture and to a fermentation process in which the apparatus is used as a control feature. This application is related to U.S. application Ser. No. 099,595 filed Sept. 22, 1987.
2. Description of the Prior Art
There is increasing interest in biotechnology, both in the traditional fermentation industry and in the exploitation of living cells in new processes to produce commercially useful products such as antibiotics, vitamins, amino acids and a variety of biologically active proteins.
The productivity of fermentation processes is dependent to a considerable extent upon culture conditions. It is therefore desirable, and has now become conventional, to control those variables such as pH and dissolved oxygen tension for which sensors are available.
One of the most important variables in a fermention process is the reactor biomass concentration, i.e. the concentration of microbial or other cells in the fermenter, since the productivity under a given set of process conditions is directly proportional to this. However, to date no accurate means has been developed for measuring the biomass content of a culture in real time, i.e. for measuring the present biomass content rather than the biomass content some time in the past.
The lack of suitable means to measure this important process variable has been commented upon by several writers in recent years, see for example: Pirt, "Principles of Microbe and Cell Cultivation", Blackwell, 1975, p 16; Carleysmith and Fox, "Fermenter Instrumentation and Control," Adv. Biotechnol. Processes 3, 1-51, 1984; and Harris and Kell, "The estimation of Microbial Biomass," Biosensors J.1, 17-84 (1985).
This last reference notes (1) that the most appropriate measure suitable for estimating biomass in real time is the biovolume, i.e. the volume fraction of a culture enclosed by the cytoplasmic membranes of the microbial or other cells within it, (2) that the only means by which biomass might be estimated in real time will be by physical as opposed to chemical measurements, and (3) that all presently available physical methods such as light scattering) for estimating biomass, are essentially unusable under the difficuclt conditions existing in a fermenter.